tbuckley/cabot-search huggingface dataset:
Patisiran Treatment in Patients with Transthyretin Cardiac Amyloidosis
Authors: Mathew S. Maurer, Parag Kale, Marianna Fontana, John L. Berk, Martha Grogan, Finn Gustafsson, Rebecca R. Hung, Robert L. Gottlieb, Thibaud Damy, Alejandra González-Duarte, Nitasha Sarswat, Yoshiki Sekijima, Nobuhiro Tahara, Mark S. Taylor, Milos Kubanek, Erwan Donal, Tomas Palecek, Kenichi Tsujita, W.H. Wilson Tang, Wen-Chung Yu, Laura Obici, Marcus Simões, Fábio Fernandes, Steen Hvitfeldt Poulsen, Igor Diemberger, Federico Perfetto, Scott D. Solomon, Marcelo Di Carli, Prajakta Badri, Matthew T. White, Jihong Chen, Elena Yureneva, Marianne T. Sweetser, Patrick Y. Jay, Pushkal P. Garg, John Vest, Julian D. Gillmore
Journal: New England Journal of Medicine (2023)

Transthyretin amyloidosis, also called ATTR amyloidosis, is associated with accumulation of ATTR amyloid deposits in the heart and commonly manifests as progressive cardiomyopathy. Patisiran, an RNA interference therapeutic agent, inhibits the production of hepatic transthyretin. Download a PDF of the Research Summary. In this phase 3, double-blind, randomized trial, we assigned patients with hereditary, also known as variant, or wild-type ATTR cardiac amyloidosis, in a 1:1 ratio, to receive patisiran (0.3 mg per kilogram of body weight) or placebo once every 3 weeks for 12 months. A hierarchical procedure was used to test the primary and three secondary end points. The primary end point was the change from baseline in the distance covered on the 6-minute walk test at 12 months. The first secondary end point was the change from baseline to month 12 in the Kansas City Cardiomyopathy Questionnaire–Overall Summary (KCCQ-OS) score (with higher scores indicating better health status). The second secondary end point was a composite of death from any cause, cardiovascular events, and change from baseline in the 6-minute walk test distance over 12 months. The third secondary end point was a composite of death from any cause, hospitalizations for any cause, and urgent heart failure visits over 12 months. A total of 360 patients were randomly assigned to receive patisiran (181 patients) or placebo (179 patients). At month 12, the decline in the 6-minute walk distance was lower in the patisiran group than in the placebo group (Hodges–Lehmann estimate of median difference, 14.69 m; 95% confidence interval [CI], 0.69 to 28.69; P=0.02); the KCCQ-OS score increased in the patisiran group and declined in the placebo group (least-squares mean difference, 3.7 points; 95% CI, 0.2 to 7.2; P=0.04). Significant benefits were not observed for the second secondary end point. Infusion-related reactions, arthralgia, and muscle spasms occurred more often among patients in the patisiran group than among those in the placebo group. In this trial, administration of patisiran over a period of 12 months resulted in preserved functional capacity in patients with ATTR cardiac amyloidosis. (Funded by Alnylam Pharmaceuticals; APOLLO-B ClinicalTrials.gov number, NCT03997383.) QUICK TAKE VIDEO SUMMARYPatisiran for Transthyretin Cardiac Amyloidosis 02:05
Inhaled Amikacin to Prevent Ventilator-Associated Pneumonia
Authors: Stephan Ehrmann, François Barbier, Julien Demiselle, Jean-Pierre Quenot, Jean-Etienne Herbrecht, Damien Roux, Jean-Claude Lacherade, Mickaël Landais, Philippe Seguin, David Schnell, Anne Veinstein, Philippe Gouin, Sigismond Lasocki, Qin Lu, Gaëtan Beduneau, Martine Ferrandiere, Gaëtan Plantefève, Claire Dahyot-Fizelier, Nader Chebib, Emmanuelle Mercier, Nathalie Heuzé-Vourc'h, Renaud Respaud, Nicolas Gregoire, Denis Garot, Mai-Anh Nay, Ferhat Meziani, Pascal Andreu, Raphaël Clere-Jehl, Noémie Zucman, Marie-Ange Azaïs, Marjorie Saint-Martin, Charlotte Salmon Gandonnière, Dalila Benzekri, Hamid Merdji, Elsa Tavernier
Journal: New England Journal of Medicine (2023)

BackgroundWhether preventive inhaled antibiotics may reduce the incidence of ventilator-associated pneumonia is unclear.MethodsIn this investigator-initiated, multicenter, double-blind, randomized, controlled, superiority trial, we assigned critically ill adults who had been undergoing invasive mechanical ventilation for at least 72 hours to receive inhaled amikacin at a dose of 20 mg per kilogram of ideal body weight once daily or to receive placebo for 3 days. The primary outcome was a first episode of ventilator-associated pneumonia during 28 days of follow-up. Safety was assessed.Download a PDF of the Research Summary.ResultsA total of 850 patients underwent randomization, and 847 were included in the analyses (417 assigned to the amikacin group and 430 to the placebo group). All three daily nebulizations were received by 337 patients (81%) in the amikacin group and 355 patients (83%) in the placebo group. At 28 days, ventilator-associated pneumonia had developed in 62 patients (15%) in the amikacin group and in 95 patients (22%) in the placebo group (difference in restricted mean survival time to ventilator-associated pneumonia, 1.5 days; 95% confidence interval [CI], 0.6 to 2.5; P=0.004). An infection-related ventilator-associated complication occurred in 74 patients (18%) in the amikacin group and in 111 patients (26%) in the placebo group (hazard ratio, 0.66; 95% CI, 0.50 to 0.89). Trial-related serious adverse effects were seen in 7 patients (1.7%) in the amikacin group and in 4 patients (0.9%) in the placebo group.ConclusionsAmong patients who had undergone mechanical ventilation for at least 3 days, a subsequent 3-day course of inhaled amikacin reduced the burden of ventilator-associated pneumonia during 28 days of follow-up. (Funded by the French Ministry of Health; AMIKINHAL ClinicalTrials.gov number, NCT03149640; EUDRA Clinical Trials number, 2016-001054-17.) Quick Take Inhaled Amikacin to Prevent Ventilator-Associated Pneumonia 1m 48s
<i>ERJ</i>Podcast October 2023: ERS short guidelines for the use of as-needed ICS/formoterol in mild asthma
Journal: European Respiratory Journal (2023)

As part of the October issue, the European Respiratory Journal presents the latest in its series of podcasts. Deputy Chief Editor Don Sin and Prof. Alberto Papi discuss the new ERS short guidelines for the use of as-needed ICS/formoterol in mild asthma.
Inotuzumab Ozogamicin as Induction Therapy for Patients Older Than 55 Years With Philadelphia Chromosome–Negative B-Precursor ALL
Authors: Matthias Stelljes, Simon Raffel, Nael Alakel, Ralph Wäsch, Mustafa Kondakci, Sebastian Scholl, Andreas Rank, Mathias Hänel, Bernd Spriewald, Maher Hanoun, Sonja Martin, Katjana Schwab, Hubert Serve, Lena Reiser, Julian Knaden, Heike Pfeifer, Julia Marx, Tim Sauer, Wolfgang E. Berdel, Georg Lenz, Monika Brüggemann, Nicola Gökbuget, Klaus Wethmar
Journal: Journal of Clinical Oncology (2023)

Despite recent advances in adapting the intensity of treatment for older patients with ALL, current protocols are associated with high rates of early deaths, treatment-related toxicity, and dismal prognosis. We evaluated inotuzumab ozogamicin and dexamethasone (Dex) as induction therapy in older patients with ALL within the German Multicenter Study Group for Adult ALL (GMALL).
The Quartet Data Portal: integration of community-wide resources for multiomics quality control
Authors: Jingcheng Yang, Yaqing Liu, Jun Shang, Qiaochu Chen, Qingwang Chen, Luyao Ren, Naixin Zhang, Ying Yu, Zhihui Li, Yueqiang Song, Shengpeng Yang, Andreas Scherer, Weida Tong, Huixiao Hong, Wenming Xiao, Leming Shi, Yuanting Zheng
Journal: Genome biology (2023)

The Quartet Data Portal facilitates community access to well-characterized reference materials, reference datasets, and related resources established based on a family of four individuals with identical twins from the Quartet Project. Users can request DNA, RNA, protein, and metabolite reference materials, as well as datasets generated across omics, platforms, labs, protocols, and batches. Reproducible analysis tools allow for objective performance assessment of user-submitted data, while interactive visualization tools support rapid exploration of reference datasets. A closed-loop "distribution-collection-evaluation-integration" workflow enables updates and integration of community-contributed multiomics data. Ultimately, this portal helps promote the advancement of reference datasets and multiomics quality control.
Endoscopy E-Videos – recently published
Journal: Endoscopy (2023)

Comment on: Peroral endoscopic myotomy to treat epiphrenic diverticulum: a step-by-step video demonstrationEndoscopy 2023; 55(S 01): E844-E845DOI: 10.1055/a-2106-1183 Comment on: Large-balloon anchor technique for endoscopic retrograde cholangiopancreatography in a patient with esophageal hiatal herniaEndoscopy 2023; 55(S 01): E858-E859DOI: 10.1055/a-2106-1967 Comment on: Cold snare and ablation technique for endoscopic mucosal resection of incompletely resected large laterally spreading tumorsEndoscopy 2023; 55(S 01): E860-E861DOI: 10.1055/a-2106-2061 Comment on: Use of a novel re-openable endoclip for the closure of a large mucosal defect after endoscopic submucosal dissectionEndoscopy 2023; 55(S 01): E883-E884DOI: 10.1055/a-2109-0883
Pumping the brakes on RNA velocity by understanding and interpreting RNA velocity estimates
Authors: Shijie C. Zheng, Genevieve Stein-O’Brien, Leandros Boukas, Loyal A. Goff, Kasper D. Hansen
Journal: Genome biology (2023)

RNA velocity analysis of single cells offers the potential to predict temporal dynamics from gene expression. In many systems, RNA velocity has been observed to produce a vector field that qualitatively reflects known features of the system. However, the limitations of RNA velocity estimates are still not well understood.
Efficacy of Testosterone Replacement Therapy in Correcting Anemia in Men With Hypogonadism
Authors: Karol M. Pencina, Thomas G. Travison, Andrew S. Artz, A. Michael Lincoff, Steven E. Nissen, Panagiotis Flevaris, Anna Chan, Xue Li, Scott A. Diegel, Kathleen Wannemuehler, Shalender Bhasin
Journal: JAMA Network Open (2023)

Importance Testosterone deficiency causes mild anemia. Whether testosterone replacement therapy (TRT) can correct anemia or prevent the development of anemia in men with hypogonadism remains incompletely understood. Objective To assess the efficacy of TRT in correcting anemia in men with hypogonadism and anemia, and reducing the risk of developing anemia in those without anemia. Design, Setting, and Participants This randomized, placebo-controlled trial included men with hypogonadism at 316 US sites enrolled between May 2018 and February 2022. This study was nested within the Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men (TRAVERSE) Study, which evaluated the effect of TRT on major adverse cardiovascular events in middle-aged and older men with hypogonadism. Eligible participants were aged 45 to 80 years, with 2 testosterone concentration results below 300 ng/dL, hypogonadal symptoms, and cardiovascular disease (CVD) or increased CVD risk. The last study visit took place in January 2023. Data were analyzed between March and August 2023. Intervention Participants were randomized with stratification for preexisting CVD to 1.62% testosterone gel or placebo gel daily for the study duration. Main Outcomes and Measures Proportion of participants with anemia (hemoglobin below 12.7 g/dL) whose anemia remitted (hemoglobin 12.7 g/dL or above) over the study duration. Secondary end points included incidence of anemia among men who were not anemic. Binary end points were analyzed using repeated-measures log-binomial regression. Results A total of 5204 men were included, 815 with anemia (mean [SD] age, 64.8 [7.7] years; 247 Black [30.3%], 544 White [66.7%], 24 other [2.9%]) and 4379 without anemia (mean [SD] age, 63.0 [7.9] years; 629 Black [14.4%], 3603 White [82.3%], 147 other [3.4%]). Anemia corrected in a significantly greater proportion of testosterone-treated than placebo-treated men at 6 months (143 of 349 [41.0%] vs 103 of 375 [27.5%]), 12 months (152 of 338 [45.0%] vs 122 of 360 [33.9%]), 24 months (124 of 290 [42.8%] vs 95 of 307 [30.9%]), 36 months (94 of 216 [43.5%] vs 76 of 229 [33.2%]), and 48 months (41 of 92 [44.6%] vs 38 of 97 [39.2%]) ( P = .002). Among participants without anemia, a significantly smaller proportion of testosterone-treated men developed anemia than placebo-treated men. Changes in hemoglobin were associated with changes in energy level. Conclusions and Relevance In middle-aged and older men with hypogonadism and anemia, TRT was more efficacious than placebo in correcting anemia. Among men who were not anemic, a smaller proportion of testosterone-treated men developed anemia than placebo-treated men. Trial Registration ClinicalTrials.gov Identifier: NCT03518034
Efficacy and safety of eltrombopag in the treatment of immune thrombocytopenia patients with hepatitis B virus infection: A prospective, multicenter, single arm, phase <scp>II</scp> trial
Authors: Yunfei Chen, Yanmei Xu, Yueting Huang, Ting Sun, Yuefen Hu, Feng Xue, Xuanwei Peng, Yinghui Lai, Zeping Zhou, Hu Zhou, Rongfu Zhou, Wei Liu, Xiaofan Liu, Huan Dong, Rongfeng Fu, Mankai Ju, Xinyue Dai, Huiyuan Li, Xiaonan Liu, Yueshen Ma, Zhen Song, Jun Peng, Renchi Yang, Lei Zhang
Journal: American Journal of Hematology (2023)

Efficacy and safety of eltrombopag in the treatment of immune thrombocytopenia patients with hepatitis B virus infection: A prospective, multicenter, single arm, phase II trialTo the Editor: Hepatitis B virus (HBV) infection is the most common chronic viral infection worldwide.Epidemiological data showed that the hepatitis virus surface antigen carrier rate among those aged 1-59 was 7.2% in China, ranking at the intermediate prevalence level. 1 Although there is no epidemiological data report on immune thrombocytopenia patients with HBV infection (ITP-HBV), previous small sample studies showed that the detection rate of anti-hepatitis B core antigen (anti-HBc) in ITP patients was 30.3%. 2 For ITP-HBV, immunosuppressive agents increase the risk of HBV reactivation.Elevating platelet counts while controlling HBV replication is the key to a good prognosis for these patients.Thrombopoietin receptor agonists (TPO-RAs) can promote bone
The value of standards for health datasets in artificial intelligence-based applications
Authors: Anmol Arora, Joseph E. Alderman, Joanne Palmer, Shaswath Ganapathi, Elinor Laws, Melissa D. McCradden, Lauren Oakden-Rayner, Stephen R. Pfohl, Marzyeh Ghassemi, Francis McKay, Darren Treanor, Negar Rostamzadeh, Bilal Mateen, Jacqui Gath, Adewole O. Adebajo, Stephanie Kuku, Rubeta Matin, Katherine Heller, Elizabeth Sapey, Neil J. Sebire, Heather Cole-Lewis, Melanie Calvert, Alastair Denniston, Xiaoxuan Liu
Journal: Nature Medicine (2023)

Abstract Artificial intelligence as a medical device is increasingly being applied to healthcare for diagnosis, risk stratification and resource allocation. However, a growing body of evidence has highlighted the risk of algorithmic bias, which may perpetuate existing health inequity. This problem arises in part because of systemic inequalities in dataset curation, unequal opportunity to participate in research and inequalities of access. This study aims to explore existing standards, frameworks and best practices for ensuring adequate data diversity in health datasets. Exploring the body of existing literature and expert views is an important step towards the development of consensus-based guidelines. The study comprises two parts: a systematic review of existing standards, frameworks and best practices for healthcare datasets; and a survey and thematic analysis of stakeholder views of bias, health equity and best practices for artificial intelligence as a medical device. We found that the need for dataset diversity was well described in literature, and experts generally favored the development of a robust set of guidelines, but there were mixed views about how these could be implemented practically. The outputs of this study will be used to inform the development of standards for transparency of data diversity in health datasets (the STANDING Together initiative).
Mucosal and Serum Antibodies 3 Weeks after Symptomatic BA.2.86 Infection
Authors: Oscar Bladh, Nina Greilert-Norin, Sebastian Havervall, Ulrika Marking, Katherina Aguilera, Jessica J. Alm, Kim Blom, Mikael Åberg, Jonas Klingström, Charlotte Thålin
Journal: New England Journal of Medicine (2023)
<i>PHF6</i>-altered T-ALL Harbor Epigenetic Repressive Switch at Bivalent Promoters and Respond to 5-Azacitidine and Venetoclax
Authors: Antoine Pinton, Lucien Courtois, Charlotte Doublet, Aurélie Cabannes-Hamy, Guillaume Andrieu, Charlotte Smith, Estelle Balducci, Agata Cieslak, Aurore Touzart, Mathieu Simonin, Véronique Lhéritier, Françoise Huguet, Marie Balsat, Hervé Dombret, Philippe Rousselot, Salvatore Spicuglia, Elizabeth Macintyre, Nicolas Boissel, Vahid Asnafi
Journal: Clinical Cancer Research (2023)

Abstract Purpose: To assess the impact of PHF6 alterations on clinical outcome and therapeutical actionability in T-cell acute lymphoblastic leukemia (T-ALL). Experimental Design: We described PHF6 alterations in an adult cohort of T-ALL from the French trial Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003/2005 and retrospectively analyzed clinical outcomes between PHF6-altered (PHF6ALT) and wild-type patients. We also used EPIC and chromatin immunoprecipitation sequencing data of patient samples to analyze the epigenetic landscape of PHF6ALT T-ALLs. We consecutively evaluated 5-azacitidine efficacy, alone or combined with venetoclax, in PHF6ALT T-ALL. Results: We show that PHF6 alterations account for 47% of cases in our cohort and demonstrate that PHF6ALT T-ALL presented significantly better clinical outcomes. Integrative analysis of DNA methylation and histone marks shows that PHF6ALT are characterized by DNA hypermethylation and H3K27me3 loss at promoters physiologically bivalent in thymocytes. Using patient-derived xenografts, we show that PHF6ALT T-ALL respond to the 5-azacytidine alone. Finally, synergism with the BCL2-inhibitor venetoclax was demonstrated in refractory/relapsing (R/R) PHF6ALT T-ALL using fresh samples. Importantly, we report three cases of R/R PHF6ALT patients who were successfully treated with this combination. Conclusions: Overall, our study supports the use of PHF6 alterations as a biomarker of sensitivity to 5-azacytidine and venetoclax combination in R/R T-ALL.
Transcatheter or Surgical Aortic Valve Replacement in Patients With Severe Aortic Stenosis and Small Aortic Annulus: A Randomized Clinical Trial
Authors: Josep Rodés-Cabau, Henrique Barbosa Ribeiro, Siamak Mohammadi, Vicenç Serra, Talal Al-Atassi, Andres Iñiguez, Victoria Vilalta, Luis Nombela-Franco, José Ignacio Sáez de Ibarra Sánchez, Vincent Auffret, Jessica Forcillo, Lenard Conradi, Marina Urena, Cesar Moris, Antonio Muñoz-Garcia, Jean-Michel Paradis, Eric Dumont, Dimitri Kalavrouziotis, Pablo Maria Pomerantzeff, Vitor Emer Egypto Rosa, Mariana Pezzute Lopes, Carles Sureda, Victor Alfonso Jimenez Diaz, Carlos Giuliani, Marisa Avvedimento, Emilie Pelletier-Beaumont, Philippe Pibarot
Journal: Circulation (2023)

The optimal treatment in patients with severe aortic stenosis and small aortic annulus (SAA) remains to be determined. This study aimed to compare the hemodynamic and clinical outcomes between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in patients with a SAA.
FDG PET/CT Image of Extramedullary Plasmacytoma in the Anterior Mediastinum
Authors: Liu Xiao, Lin Li
Journal: Clinical Nuclear Medicine (2023)

Extramedullary plasmacytoma in the anterior mediastinum is very rare. We report FDG PET/CT findings of anterior mediastinum extramedullary plasmacytoma in a 54-year-old woman. On FDG PET/CT, it presented as a solitary anterior mediastinum mass with increased FDG uptake. The final pathology supported a diagnosis of extramedullary plasmacytoma. This case hints us that extramedullary plasmacytoma should be regarded as a differential diagnosis when we encounter a solitary anterior mediastinum mass with intense FDG uptake.
Giant Fibrovascular Polyp Mimicking Esophageal Malignancy on 18F-FDG PET/CT
Authors: MinJeong Kim, Kum Ju Chae, Jong-Hun Kim, Yeon-Hee Han
Journal: Clinical Nuclear Medicine (2023)

A 52-year-old man presented with continuous dull pain from the throat to the epigastric region with dysphagia. Initial endoscopy misdiagnosed a subepithelial tumor causing external compression of the esophagus. A CT scan visualized a 14.0 × 4.0-cm pedunculated mass inside the esophagus. Subsequent 18 F-FDG PET/CT identified an intense FDG-avid area in the mass, which strongly suggested esophageal cancer. Total mass excision was performed, and fibrovascular polyp with chronic ulcerative inflammation was finally confirmed on histologic examination.
Jen Gommerman: Leadership is not a one-way street
Authors: Lucie Van Emmenis
Journal: The Journal of Experimental Medicine (2023)

Jen Gommerman is a Canada Research Chair in Tissue Specific Immunity, and a professor and newly appointed chair for the Department of Immunology at the University of Toronto. Her lab is interested in the underlying mechanisms of immune dysregulation in autoimmune diseases such as MS, mucosal immunology, and the role of TNF family members in immune cell biology. We spoke to Jen about the importance of authenticity and openness in leadership, and her goals as she begins her tenure as department chair of Immunology.
MDM2 Regulation of HIF Signaling Causes Microvascular Dysfunction in Hypertrophic Cardiomyopathy
Authors: Puneeth Shridhar, Michael S. Glennon, Soumojit Pal, Christina J. Waldron, Ethan J. Chetkof, Payel Basak, Nicolas G. Clavere, Dipanjan Banerjee, Sebastien Gingras, Jason R. Becker
Journal: Circulation (2023)

Microvasculature dysfunction is a common finding in pathologic remodeling of the heart and is thought to play an important role in the pathogenesis of hypertrophic cardiomyopathy (HCM), a disease caused by sarcomere gene mutations. We hypothesized that microvascular dysfunction in HCM was secondary to abnormal microvascular growth and could occur independent of ventricular hypertrophy.
Testosterone Replacement in Men With Hypogonadism and Effects on Anemia—Blood, Sex, and Aging
Authors: Shabbir M. H. Alibhai
Journal: JAMA Network Open (2023)

Karol M. Pencina, PhD; Thomas G. Travison, PhD; Andrew S. Artz, MD, MS; A. Michael Lincoff, MD; Steven E. Nissen, MD; Panagiotis Flevaris, MD, PhD; Anna Chan, PharmD; Xue Li, PhD; Scott A. Diegel, MS; Kathleen Wannemuehler, PhD; Shalender Bhasin, MB, BS
Oxygenated Scaffolds for Pancreatic Endocrine Differentiation from Induced Pluripotent Stem Cells
Authors: Hui Huang, Soujanya S. Karanth, Ya Guan, Sebastian Freeman, Ryan Soron, David S. Godovich, Jianjun Guan, Kaiming Ye, Sha Jin
Journal: Advanced Healthcare Materials (2023)

Abstract A 3D microenvironment is known to endorse pancreatic islet development from human induced pluripotent stem cells (iPSCs). However, oxygen supply becomes a limiting factor in a scaffold culture. In this study, oxygen‐releasing biomaterials are fabricated and an oxygenated scaffold culture platform is developed to offer a better oxygen supply during 3D iPSC pancreatic differentiation. It is found that the oxygenation does not alter the scaffold's mechanical properties. The in situ oxygenation improves oxygen tension within the scaffolds. The unique 3D differentiation system enables the generation of islet organoids with enhanced expression of islet signature genes and proteins. Additionally, it is discovered that the oxygenation at the early stage of differentiation has more profound impacts on islet development from iPSCs. More C‐peptide + /MAFA + β and glucagon + /MAFB + α cells formed in the iPSC‐derived islet organoids generated under oxygenated conditions, suggesting enhanced maturation of the organoids. Furthermore, the oxygenated 3D cultures improve islet organoids’ sensitivity to glucose for insulin secretion. It is herein demonstrated that the oxygenated scaffold culture empowers iPSC islet differentiation to generate clinically relevant tissues for diabetes research and treatment.